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Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease
Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL, Jicha GA, Karydas AM et al.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016-09-06
Topic: Brain proteins, microglia and lab models
Synaptic dysfunction occurs early in senile dementias, presumably as a result of decreased levels of functional synaptic proteins as found in autopsied brains of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD). Plasma neuronal-derived exosomes (NDEs) were recovered by precipitation and immunoabsorption from 12 patients with AD, 16 with FTD, and 28 controls in a cross-sectional study, and from 9 patients with AD, 10 with FTD, and 19 controls in a longitudinal study. Six synaptic proteins in NDE extracts were quantified by ELISAs and normalized for exosome amounts. NDE levels of synaptophysin, synaptopodin, synaptotagmin-2, and neurogranin were significantly lower in patients with FTD and AD than in controls, but those of growth-associated protein 43 and synapsin 1 were reduced only in patients with AD. Functionally relevant phosphorylation of synapsin 1 serine 9 was reduced in patients with FTD and AD, although total synapsin 1 protein was higher in FTD than in controls. NDE levels of synaptotagmin, synaptophysin, and neurogranin were decreased years before dementia in patients with FTD and AD. NDE levels of synaptopodin, synaptotagmin, and synaptophysin, but not of amyloid β-peptide 42 or P-T181-tau, were correlated significantly with cognition assessed by mini-mental state examination or AD assessment scale-cognitive subscale. NDE synaptic proteins may be useful preclinical indices and progression measures in senile dementias.-Goetzl, E. J., Kapogiannis, D., Schwartz, J. B., Lobach, I. V., Goetzl, L., Abner, E. L., Jicha, G. A., Karydas, A. M., Boxer, A., Miller, B. L. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease.
Key findings
- Synaptic dysfunction occurs early in senile dementias, presumably as a result of decreased levels of functional synaptic proteins as found in autopsied brains of patients with Alzheimer's disease (AD) or frontotemporal dementia (FTD).
- NDE levels of synaptophysin, synaptopodin, synaptotagmin-2, and neurogranin were significantly lower in patients with FTD and AD than in controls, but those of growth-associated protein 43 and synapsin 1 were reduced only in patients with AD.
- NDE levels of synaptopodin, synaptotagmin, and synaptophysin, but not of amyloid β-peptide 42 or P-T181-tau, were correlated significantly with cognition assessed by mini-mental state examination or AD assessment scale-cognitive subscale.
Why it matters
In this cross-sectional and longitudinal study, plasma neuronal-derived exosome levels of several synaptic proteins were significantly lower in Alzheimer's disease and frontotemporal dementia patients than in controls, and some were decreased years before dementia. These proteins correlated with cognition and may serve as biomarkers, but no treatment, cure, or prevention is reported.
Study details
- Study designcross-sectional
- Participants12
- Evidence strengthModerate
How this study scored 63/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (FASEB journal : official publication of the Federation of American Societies for Experimental Biology) |
| Journal's citation record | 3 / 4 | The FASEB Journal: journal h-index 401 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 12 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 397 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 33.1 citations a year over 12 year(s) since 2016 |
| Impact for its field and year | 5 / 6 | Cited 20.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 109 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bruce L. Miller: h-index 198 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27601437) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Goetzl, E. J., Kapogiannis, D., Schwartz, J. B., Lobach, IV., Goetzl, L., Abner, E. L., et al. (2016). Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.201600816r
Vancouver
Goetzl EJ, Kapogiannis D, Schwartz JB, Lobach IV, Goetzl L, Abner EL, et al. Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2016. doi:10.1096/fj.201600816r. PMID: 27601437.
BibTeX
@article{goetzl2016-27601437,
author = {Goetzl, E. J. and Kapogiannis, D. and Schwartz, J. B. and Lobach, IV. and Goetzl, L. and Abner, E. L. and Jicha, G. A. and Karydas, A. M. and others},
title = {{Decreased synaptic proteins in neuronal exosomes of frontotemporal dementia and Alzheimer's disease}},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2016},
doi = {10.1096/fj.201600816r},
pmid = {27601437},
url = {https://doi.org/10.1096/fj.201600816r}
}
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